OPTHALMIC DOSAGE FORM

PRESENTED BY

VARSHA AWASARKAR

Ophthalmic preparations DEFINATION:

“Ophthalmic preparation is sterile product that is intended to be applied to the eyelids or placed in the space between the eyelids and the eyeball.”

They are specialized dosage forms designed to be instilled onto the external surface of the eye (topical), administered inside (intraocular) or adjacent (periocular) to the eye or used in conjunction with an ophthalmic device.

A drug delivery to circumvent ailments of the eye.

A challenge to formulator is to avoid a protective barrier of the eye.

• Need of a successful design.

OCULAR ANATOMY AND PHYSIOLOGY

Fig. Anatomy and Physiology of the Eye

BARRIERS IN OCULAR ABSORPTION

It includes-

• Solution drainage

• Cornea as rate limiting barrier

• Lachrymation

• Anatomy of cornea

• Tear dilution 1. Outer-Epithelium (lipophilic)

2. Middle-Stroma (hydrophilic), Conjunctival

absorption

3. Inner-Endothelium (lipophilic )

Precorneal constraints

Corneal constraints

Drugs used in the eye

• Miotics e.g. pilocarpine Hcl• Mydriatics e.g. Atropine• Cycloplegics e.g. atropine• Anti-inflammatory e.g. corticosteroids• Anti-infectives (antibiotics, antivirals and antibacterials)• Anti-glucoma drugs e.g. pilocarpine Hcl• Surgical adjuncts e.g. irrigating solutions• Diagnostic drugs e.g. sodiumfluorescein• Anesthetics e.g. tetracaine

Sterility

Corneal absorption

Figure. Some of the routes of administration in the eye.

Cont…….

CLASSIFICATION OF OCULAR DRUG DELIVERY SYSTEMS:

B. Manufacturing Techniques:

Aqueous ophthalmic solutions:

Aqueous suspensions

Ophthalmic ointment

Gels

• Ophthalmic gels are composed of mucoadhesive polymers that provide localized delivery of an active ingredient to the eye. Such polymers have a property known as bioadhesion meaning attachment of a drug carrier to a specific biological tissue.

• These polymers are able to extend the contact time of the drug with the biological tissues and thereby improve ocular bioavailability. The choice of the polymer plays a critical role in the release kinetics of the drug(s) from the dosage form. Several bioadhesive polymers are available with varying degree of mucoadhesive performance.

• Some examples are carboxymethylcellulose, carbopol, polycarbophil, and sodium alginate.

Emulsions

• Topical ophthalmic emulsions generally are prepared by dissolving or dispersing the active ingredient(s) into an oil phase, adding suitable emulsifying and suspending agents and mixing with water vigorously to form a uniform oil-in-water emulsion.

• Each phase is typically sterilized prior to or during charging into the mixing vessel.

• High-shear homogenation may be employed to reduce oil droplet size to sub-micron size which may improve the physical stability of the oil micelles so they do not coalesce.

Cont…

• The resulting dosage form should contain small

oil droplets, uniformly suspended.

• To prevent flocculation, creaming and

coalescence of the emulsions, manufacturers

commonly add surfactants to increase the

kinetic stability of the emulsion so that the

emulsion does not change significantly with time.

Strips• Ophthalmic strips are made of

filter paper and are individually packed to ensure sterility until the time of use.

• They can be used in the measurement of tear production in dry eye conditions.

• E.g. fluorescein sodium used as a diagnostic strips to visualize defects or aberrations in the corneal epithelium by staining the areas of cellular loss.

Injections

• While injections are considered a dosage form for nomenclature purposes, they are not treated as a dosage form in this paper.

• Instead, refer to the appropriate physical form, such as, suspension, etc., for general information.

OCUSERTS Ocular inserts are defined as preparations with a solid or semisolid consistency, whose size and shape are especially designed for ophthalmic application (i.e., rods or shields). These inserts are placed in the lower fornix and, less frequently, in the upper fornix or on the cornea. They are usually composed of a polymeric vehicle containing the drug and are mainly used for topical therapy.

The mechanism of controlled drug release into the eye is as follows:

A. Diffusion, B. Osmosis, C. Bio-erosion

OCUFIT SROCUFIT SR

ADVANTAGES:

Low dose.

Control release.

Patient compliance.

DISADVANTAGES:

Costly

Retain in eye for 7 days.

Periodic check.

Replacement of contaiminated unit with fresh one.

Challenging to position into eye

CONTACT LENS• Contact lenses can be a way of

providing extended release of drugs into the eye.

• Conventional hydrogel soft contact lenses have the ability to absorb some drugs and release them into the postlens lachrymal fluid, minimizing clearance and sorption through the conjunctiva.

• Their ability to be a drug reservoir strongly depends on the water content and thickness of the lens, the molecular weight of the drug, the concentration of the drug loading solution and the time the lens remains in it.

• The ability of contact lens to load drugs and to

control their release is in general inadequate and

the following approaches, based on modifications

of the polymer network, are under evaluation:

(1) Covalent binding of the drug to the lens network via labile bonds;

(2) Inclusion of the drug in colloidal structures that are dispersed in the

lens and are responsible for controlling drug release;

(3) Functionalization of the network with chemical groups that work as

ion-exchange resins; and

(4) Creation in the lens structure of imprinted pockets that memorize the

spatial features and bonding preferences of the drug and provide the

lens with a high affinity and selectivity for a given drug.

IMPLANTS• Implants have been widely employed

to extend the release of drugs in ocular fluids and tissues particularly in the posterior segment. Implants can be broadly classified into two categories based on their degradation properties:

(1) biodegradable and

(2) nonbiodegradable• With implants, the delivery rate could

be modulated by varying polymer composition.

• Implants can be solids, semisolids or particulate-based delivery systems.

DRUG RELEASE KINETICS

The mathematical models are used to evaluate the kinetics and mechanism of drug release from the tablets.

The model that best fits the release data is selected based on the correlation coefficient (r) value in various models.

The model that gives high ‘r’ value is considered as the best fit of the release data.

Mathematical models

1)Zero order release model

2)First order release model

3)Hixson-crowell release model

4)Higuchi release model

5)Korsmeyer – peppas release model

ZERO ORDER RELEASE EQUATION

• The equation for zero order release is

Qt = Q0 + K0 t

where

Q0 = initial amount of drug

Qt = cumulative amount of drug release at time “t”

K0 = zero order release constant

t = time in hours

• It describes the systems where the drug release rate is independent of its concentration of the dissolved substance.

• A graph is plotted between the time taken on x-axis and the cumulative percentage of drug release on y-axis and it gives a straight line.

FIRST ORDER RELEASE EQUATION

• The first order release equation is

Log Qt = Log Q0+ Kt /2.303 

where

Q0 = initial amount of drug

Qt = cumulative amount of drug release at time “t”

K = first order release constant

t = time in hours

• Here, the drug release rate depends on its concentration

• A graph is plotted between the time taken on x-axis and the log cumulative percentage of drug remaining to be released on y-axis and it gives a straight line.

HIXSON - CROWELL RELEASE EQUATION

• The Hixson - Crowell release equation is

Where

Q0 = Initial amount of drug

Qt = Cumulative amount of drug release at time “t”

KHC = Hixson crowell release constant

t = Time in hours.

• It describes the drug releases by dissolution and with the changes in surface area and diameter of the particles or tablets

• A linear plot of the cube root of the initial concentration minus the cube root of percent remaining versus time in hours for the dissolution data in accordance with the Hixson-crowell equation.

HIGUCHI RELEASE EQUATION

• The Higuchi release equation is

Q=KHt1/2

where

Q = cumulative amount of drug release at time “t”

KH = Higuchi constant

t = time in hours

• The Higuchi equation suggests that the drug release by diffusion.

• A graph is plotted between the square root of time taken on x-axis and the cummulative percentage of drug release on y-axis and it gives a straight line.

KORSMEYER-PEPPAS EQUATION

• Korsmeyer – peppas equation is

F = (Mt /M ) = Kmtn

Where

F = Fraction of drug released at time ‘t’

Mt = Amount of drug released at time ‘t’

M = Total amount of drug in dosage form

Km = Kinetic constant

n = Diffusion or release exponent

t = Time in hours

• ‘n’ is estimated from linear regression of log ( Mt/M ) versus log t

• If n = 0.45 indicates fickian diffusion

• 0.45<n<0.89 indicates anomalous diffusion or non-fickian diffusion.

• If n = 0.89 and above indicates case-2 relaxation or super case transport-2.

• Anomalous diffusion or non-fickian diffusion refers to combination of both diffusion and erosion controlled rate release.

• Case-2 relaxation or super case transport-2 refers to the erosion of the polymeric chain.

• A graph is plotted between the log time taken on x-axis and the log cummulative percentage of drug release on y-axis and it gives a straight line.